This program will continue to use the power of molecular biology to develop and test new molecular markers for the early detection of NSCLC. As an interactive project, this study brings together promising new approaches from various investigators to develop new molecular markers garnished form some of the most promising areas of genetic research. Novel markers will continue to be developed by 1) differential chip expression studies 2) discovery of additional methylated gene promoters and development of MSP and QMSP assays and 3) identification of mitochondrial DNA mutations. These approaches have already yielded hundreds of promising markers and a robust pipeline for marker development including markers currently in late stage validation trials in the EDRN. We will now place more emphasis will be place on continued development of newly discovered markers into additional analytical and clinical validation. By continuing to integrate these promising approaches from diverse labs at Hopkins we will continue to develop a comprehensive profile of markers in lung cancer. Bronchoalveolar lavage samples and serum/plasma samples from cases and controls will allow us to test new markers directly in rapid pilot studies. As shown previously, we will extend our work in other tumor types when indicated and will share markers and technologies with other EDRN sites. Unlike the usual approach of marker discovery among individual investigators, this integrated project emphasizes the sharing of subjects, tissues, resources, technical expertise and data analysis strategies. Our integrated efforts offer clinical direction and facilitate the translation of basic discoveries in the lab into the clinical arena by further leveraging the unique resources of the entire EDRN.